Device for collecting skin permeable gas and apparatus for measuring skin permeable gas

ABSTRACT

An apparatus for measuring skin permeable gas, which can be used to obtain clinical information by noninvasive and bloodless operations and are useful for in-home medical care and health management. The device for collecting skin permeable gas includes a cylindrical member including a spiral groove, a cover disposed on the upper surface of the cylindrical member, a gas-introducing section connected to the cover, a gas delivery section connected to the cover, and a sealing member for sealing the groove of the cylindrical member and for maintaining air contained in the groove at a predetermined temperature. After components in the air maintained at a predetermined temperature are analyzed, the sealing member is detached from the cylindrical member and the cylindrical member from which the sealing member is detached is then brought into intimate contact with skin of a subject to collect the skin permeable gas.

TECHNICAL FIELD

The present invention relates to a device for collecting skin permeablegas and an apparatus for measuring such skin permeable gas, wherein thedevice and apparatus are used to determine the health condition ofsubjects.

BACKGROUND ART

Conventionally, blood and human metabolites (urine and feces) have beenmajor clinical items used for determining human health condition.Recently, saliva and expired gas have been becoming test objects, andsweat will be also included in such clinical items in future. Componentsof such expired gas, saliva, and sweat depend on components of blood andthus there is quantitative relationship between both the components. Itis expected that these noninvasive metabolites be used in the field ofin-home medical care and health management in future.

There have been no measuring equipment used for clinical measurement andno measuring equipment for determining human health condition using suchskin permeable gas. This is because the existence of the skin permeablegas itself has not been assumed for such purposes.

DISCLOSURE OF INVENTION

As described above, the inventors have found that skin permeable gasdepends on components of blood in peripheral blood vessels. Theinventors have also found that the skin permeable gas is extremelyimportant in determining new types of morbidity.

In view of the above situation, it is an object of the present inventionto provide an apparatus for measuring the skin permeable gas, whereinsuch an apparatus can be used to obtain clinical information bynoninvasive and bloodless operations and is useful for in-home medicalcare and health management.

In order to achieve the above object, the following devices andapparatus are provided.

(1) A skin permeable gas-collecting device including a container havingan opening section and including a storing means for storing skinpermeable gas emanating from skin, the skin permeable gas being obtainedby bringing the opening section into intimate contact with the skin; anda delivery means for delivering the skin gas stored in the container.

(2) The skin permeable gas-collecting device further including apartition, disposed at a lower section inside the container, having anopening at the center thereof; and an operating member for opening andclosing the opening of the partition.

(3) The skin permeable gas-collecting device, wherein the containerincludes a first sub-container, having a hole, for storing the skinpermeable gas; a second sub-container that surrounds the firstsub-container and is brought into intimate contact with the skin bydecompression obtained by removing air; and a delivery unit fordelivering the skin permeable gas stored in the first sub-container.

(4) A skin permeable gas-collecting device including a finger-stallincluding a coupler, and one or more connections that are connectablewith the coupler and include a stopcock.

(5) A skin permeable gas-collecting device including a cylindricalmember including a spiral groove, a cover disposed on the upper surfaceof the cylindrical member, a gas-introducing section connected to thecover, a gas delivery section connected to the cover, and a sealingmember for sealing the groove of the cylindrical member and formaintaining air contained in the groove at a predetermined temperature,wherein, after components in the air maintained at a predeterminedtemperature are analyzed, the sealing member is detached from thecylindrical member and the cylindrical member from which the sealingmember is detached is then brought into intimate contact with skin of asubject to collect the skin permeable gas.

(6) A skin permeable gas-measuring apparatus including a firstcontainer, having an opening, for storing skin permeable gas; a blowerfan for circulating the stored skin permeable gas; and a measuring unitincluding a coloring agent placed in a path through which the gas iscirculated with the blower fan.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an illustration showing a configuration of a skin permeablegas-collecting device according to a first example of the presentinvention.

FIG. 2 is an illustration showing a configuration of a skin permeablegas-collecting device according to a second example of the presentinvention.

FIG. 3 is an illustration showing a configuration of a skin permeablegas-collecting device according to a third example of the presentinvention.

FIG. 4 is an illustration showing a comparison between the acetonecontent in expired gas and the acetone content in vapor emanating from aleft index finger.

FIG. 5 is an illustration showing a configuration of a skin permeablegas-collecting device (sampling probe) according to a fourth example ofthe present invention.

FIG. 6 is an illustration showing the relationship between the quantityof emitted acetone and BMI, wherein the acetone quantity is obtainedwith a device of the present invention and BMI is an obesity index.

FIG. 7 is an illustration showing chromatograms of a probe blank of thepresent invention which is obtained by performing sampling inside a leftforearm for ten minutes.

FIG. 8 is an illustration (first illustration) showing the relationshipbetween the ingestion of milk and the quantity of emitted hydrogen gascollected with a skin permeable gas-collecting device of the presentinvention; between the ingestion of milk and the quantity of thehydrogen gas in expired gas after the ingestion of milk.

FIG. 9 is an illustration (second illustration) showing the relationshipbetween the ingestion of milk and the quantity of emitted hydrogen gascollected with a skin permeable gas-collecting device of the presentinvention; between the ingestion of milk and the quantity of thehydrogen gas in expired gas after the injection of milk.

FIG. 10 is an illustration (third illustration) showing the relationshipbetween the ingestion of milk and the quantity of emitted hydrogen gascollected with a skin permeable gas-collecting device of the presentinvention; between the ingestion of milk and the quantity of thehydrogen gas in expired gas after the ingestion of milk.

FIG. 11 is an illustration (fourth illustration) showing therelationship between the ingestion of milk and the quantity of emittedhydrogen gas collected with a skin permeable gas-collecting device ofthe present invention; between the ingestion of milk and the quantity ofthe hydrogen gas in expired gas after the ingestion of milk.

FIG. 12 is an illustration showing a configuration of a skin permeablegas-measuring apparatus according to a fifth example of the presentinvention.

BEST MODE FOR CARRYING OUT THE INVENTION

Embodiments of the present invention will now be described in detailwith reference to the accompanying drawings.

FIG. 1 is an illustration showing a configuration of a skin permeablegas-collecting device according to a first example of the presentinvention. FIG. 1(a) is a perspective view showing the outline thereof,FIG. 1(b) is an illustration showing such a state that a lower chamberof the skin permeable gas-collecting device is filled with skinpermeable gas, FIG. 1(c) is an illustration showing such a state thatthe skin permeable gas is allowed to flow into an upper chamber from thelower chamber, and FIG. 1(d) is an illustration showing such a statethat the upper chamber filled with the skin permeable gas is sealed.

In these figures, reference numeral 1 represents a container of the skinpermeable gas-collecting device; reference numeral 1A represents a lowerchamber disposed in the container 1; reference numeral 1B represents anupper chamber disposed in the container 1; reference numeral 2represents a partition plate, disposed at a lower position inside thecontainer 1, having an opening 2A at the center thereof; referencenumeral 3 represents an operating member capable of opening and closingthe opening 2A of the partition plate 2; reference numeral 4 representsa knob disposed at the upper end of the operating member 3; referencenumeral 5 represents a rod of the operating member 3; reference numeral6 represents a valve member disposed at the lower end of the rod 5;reference numeral 7 represents an O-ring for sealing a gap between thecontainer 1 and the rod 5; reference numeral 8 represents a ventilationport, connected to the container 1, for removing the skin permeable gas;reference numeral 9 represents a delivery port, connected to thecontainer 1, for removing the skin permeable gas; and reference numeral10 represents skin of a subject.

The operation of this device is described below.

As shown in FIG. 1(b), the container 1 of the skin permeablegas-collecting device is pressed against the subject skin 10 and thenfixed thereto in such a state that the operating member 3 is presseddownward and thereby the opening 2A of the partition plate 2 is stoppedup with the valve member 6. In such a state, skin permeable gasemanating from the subject skin 10 is collected in the lower chamber 1A.The ventilation port and the delivery port 9 for removing the skinpermeable gas are closed, wherein the ventilation port and the deliveryport 9 are connected to the container 1.

After the collection of the skin permeable gas is finished, theoperating member 3 is drawn up to open the opening 2A of the partitionplate 2, as shown in FIG. 1(c). Thereby, the skin permeable gascollected in the lower chamber 1A is allowed to flow into the upperchamber 1B.

As shown in FIG. 1(d), the operating member 3 is pressed down again toclose the opening 2A of the partition plate 2 and thereby the skinpermeable gas is trapped and stored in the upper chamber 1B.

The delivery port 9 for the skin permeable gas is opened, theventilation port 8 is also opened, and gas is fed from the ventilationport 8 to force the skin permeable gas out, thereby subjecting the skinpermeable gas to measurement. This procedure, however, is not shown inthe figure.

FIG. 2 is an illustration showing a configuration of a skin permeablegas-collecting device according to a second example of the presentinvention.

In this figure, reference numeral 11 represents a first container forstoring the skin permeable gas; reference numeral 12 represents a secondcontainer, surrounding the first container 11 for removing air toprovide decompression to bring the first container 11 into intimatecontact with skin; reference numeral 13 represents an evacuation unit,connected to the second container 12, for removing gas; referencenumeral 14 represents a cock; reference numeral 15 represents agas-introducing unit connected to the first container 11; referencenumeral 16 represents a delivery unit, connected to the first container11, for removing the skin permeable gas; and reference numeral 17represents skin of a subject.

According to the above configuration, after the delivery unit 16 isclosed and the gas-introducing unit 15 is opened to introduce gas (dryair) into the first container 11, the gas-introducing unit 15 is closedto collect the skin permeable gas from the subject skin 17. After theskin permeable gas is collected, the delivery unit 16 is opened todeliver the skin permeable gas into a test container (not shown).

In this case, in order to bring the first container 11 into intimatecontact with the subject skin 17, the container section has dualstructure. In particular, the second container 12 arranged outside thefirst container 11 is decompressed with the evacuation unit 13, therebybringing the first container 11 into intimate contact with the skin.

FIG. 3 is an illustration showing a configuration of a skin permeablegas-collecting device according to a third example of the presentinvention. FIG. 3(a) is an illustration showing a finger-stall and aninjection syringe connected thereto, FIG. 3(b) is an illustrationshowing such a situation that a finger is fitted into the finger-stall,FIG. 3(c) is an illustration showing such a situation that thefinger-stall is filled with air fed from the injection syringe, and FIG.3(d) is an illustration showing such a situation that the air and skinpermeable gas are inhaled.

In these figures, reference numeral 21 represents a finger-stall (a bagmade from Teflon), reference numeral 22 represents a coupler (forexample, a cock), reference numeral 23 represents an injection syringe(100 ml), reference numeral 24 represents a stopcock, reference numeral25 represents rubber or a clip provided on the outside of the base ofthe finger-stall 22, reference numeral 26 represents a finger of asubject, reference numeral 27 represents a gas-introducing unit, andreference numeral 28 represents the inflated finger-stall filled withair.

According to this example, the skin permeable gas can be recovered bythe following methods.

(1) First Method

As shown in FIG. 3(a), the following tools are prepared: thefinger-stall 21 having the cock 22 at the tip thereof and the injectionsyringe 23, connectable to the cock 22, including the stopcock 24. Asshown in FIG. 3(b), the finger 26 is fitted into the finger-stall 21. Asshown in FIG. 3(c), the stopcock 24 is opened, the cock 22 is thenopened to introduce gas (dry air) from the injection syringe 23, thefinger-stall 21 is inflated and then sealed, and the stopcock 24 is thenclosed. Subsequently, the skin permeable gas is collected from thesubject finger 26. After the collection of the skin permeable gas, thestopcock 24 is opened to deliver (recover) the collected skin permeablegas into injection syringe 23 through the cock 22.

(2) Second Method

As shown in FIG. 3(a), the following tools are prepared: thefinger-stall 21 having the cock 22 at the tip thereof and the injectionsyringe 23, connectable to the cock 22, including the stopcock 24. Asshown in FIG. 3(b), the finger 26 is fitted into the finger-stall 21. Asshown in FIG. 3(c), the stopcock 24 is closed, the gas-introducing unit27 is opened to introduce gas (dry air), the finger-stall 21 is inflatedand then sealed, thereby collecting the skin permeable gas. After thecollection of the skin permeable gas, the stopcock 24 is opened torecover the collected skin permeable gas into injection syringe 23through the cock 22.

(3) Third Method

As shown in FIG. 3(a), the following tools are prepared: thefinger-stall 21 having the cock 22 at the tip thereof and the injectionsyringe 23, connectable to the cock 22, including the stopcock 24. Asshown in FIG. 3(b), the finger 26 is fitted into the finger-stall 21. Asshown in FIG. 3(c), the stopcock 24 is opened, and the skin permeablegas is collected in the injection syringe 23 while the gas-introducingunit 27 is opened to introduce gas (dry air).

The collecting procedure is not limited to the above methods. Variousmodifications including the following procedures may be performed: aprocedure in which gas is introduced from the cock 22 to collect theskin permeable gas and the skin permeable gas is then recovered(delivered) into the injection syringe 23 and a procedure in which gasis introduced from the gas-introducing unit 27 to collect the skinpermeable gas and the skin permeable gas is then recovered through thecock 22.

According to the above configuration, emitted gas can be readilycollected from the body skin surface, for example, the finger skinsurface, which is herein used, and then recovered (delivered).

Examples according to the collecting procedure will now be described.

FIG. 4 is an illustration showing a comparison between the acetonecontent in expired gas and the acetone content in vapor emanating from aleft index finger.

Acetone emanating from the left index finger was collected and theexpired gas was also collected at the time when the acetone sampling isstated. The comparison result of the acetone content is shown in FIG. 4.As shown in this figure, there is a positive correlation between theacetone content in the expired gas and the acetone content in the vaporemanating from the left index finger.

When the acetone emanating from the left index finger was collectedaccording to the above procedure and then determined, the outside airwas used in this procedure. This is because the outside air inevitablyleaks into the finger-stall when the finger is fitted into thefinger-stall during the sampling.

This procedure was employed on the premise that the acetone content inthe outside air does not change for a short period (within 30 minutes).Since the acetone content does not inevitably remain constant in actual,this procedure for determining the acetone content is not precise if achange in the acetone content exceeds allowable limits. In order tosolve this problem, the following finger-stall and sampling proceduremust be employed: a finger-stall into which the outside air does notleak when a finger is fitted into or drawn out of the finger-stall, anda sampling procedure using such a finger-stall.

FIG. 5 is an illustration showing a configuration of a skin permeablegas-collecting device (sampling probe) according to a fourth example ofthe present invention.

In this figure, reference numeral 31 represents a cylindrical memberhaving a spiral groove 32; reference numeral 33 represents a coverplaced on the upper face of the cylindrical member 31; reference numeral34 represents a gas-introducing section connected to the cover 33;reference numeral 35 represents a gas delivery section connected to thecover 33; reference numeral 40 represents a sealing member, connected tothe cylindrical member, for sealing the groove 32 of the cylindricalmember 31 and for maintaining air contained in the groove 32 at apredetermined temperature; reference numeral 41 represents a heat sink;reference numeral 42 represents a Peltier element for adjusting thetemperature of the contained air; reference numeral 43 represents asilicon coating; and reference numeral 44 represents a Teflon sheet forsealing the groove 32 containing the air.

Air in a laboratory room is introduced into the cylindrical member 31from the gas-introducing section 34 and then stored therein, thetemperature of the introduced air is adjusted to a predetermined valuewith the Peltier element 42, and the resulting air is delivered throughthe gas delivery section 35, thereby subjecting the air (probe blank) tomeasurement. Replacing the sealing member 40 connected to thecylindrical member in the situation, the bottom face of the cylindricalmember 31 is pressed against skin of a subject 45 to collect skinpermeable gas in the groove 32 of the cylindrical member 31 in a sealedmanner while the above situation is maintained except that the sealingmember 40 of the cylindrical member is not used. The collected skinpermeable gas is delivered together with air through the gas deliverysection 35 and is then subjected to measurement.

The measurement result is described below.

Table 1 shows the measurement result. Value Obtained Value Obtained fromMeasuring from Human Skin Actual Quantity Tool (Air + Skin Obtained fromHuman (Air Only) Permeable Gas) Human Skin a 1.8 4.4 2.6 b 3.3 7.6 4.3c** 3.1 11.7 8.6 d** 4.5 14.0 9.5 e** 3.9 9.1 5.2 f 4.9 7.7 2.8 g** 2.012.6 10.6

As shown in this table, for Subject a, the air quantity obtained from ameasuring tool is 1.8 ng, and the total quantity of air and acetone is4.4 ng, the acetone being skin permeable gas emanating from the subject.Thus, the quantity of acetone gas emanating from the skin surface of thesubject is 2.6 ng. In any subject, sampling data obtained from skin hasa higher value than that of the probe blank.

The acetone content in 50 ml, 25 ml, and 10 ml of room air is 5.8, 2.8,and 1.3 ng, respectively. Since the volume of the sampling probe is 3.8ml, the quantity of contaminants leaking from the surroundings is 0.5 ngor less. The acetone content in air of the laboratory room issubstantially equal to that in room air in a reinforced concretebuilding.

It can be inferred from the above result that the quantity of acetoneemanating from a human skin surface can be measured with this experimentmeans.

FIG. 6 is an illustration showing the relationship between the quantityof emitted acetone and BMI (body mass index, defined as the formula:body weight (kg)/(body height (m))²), wherein the acetone quantity isobtained with a device of the present invention and BMI is an obesityindex.

It is clear from this figure that there is a positive correlationbetween the obesity index (BMI) and the quantity of emitted acetone.

Gas collected from a human skin surface is analyzed by, for example,chromatography.

FIG. 7 is an illustration showing the result of chromatography analysisof a probe blank of the present invention which is obtained byperforming sampling inside a left forearm for one minute. The uppersection of FIG. 7 is an illustration showing the result of thechromatography analysis of gas obtained by performing sampling inside aleft forearm for ten minutes using a skin permeable gas-collectingdevice of the present invention. The lower section of FIG. 7 is anillustration showing the result of the chromatography analysis of theprobe blank. It is clear from this figure that the quantity of the skinpermeable gas emanating from the human skin surface is larger than thatof the gas remaining in the surroundings and the probe blank.

FIGS. 8 to 11 are illustrations showing the relationship between theingestion of milk and the quantity of emitted hydrogen gas collectedwith a skin permeable gas-collecting device of the present invention;between the ingestion of milk and the quantity of the hydrogen gas inexpired gas after the ingestion of milk. The illustrations showchromatograms obtained by measuring the hydrogen content in thefollowing cases: an expired gas and a gas obtained from the left hand ofSubject A (before the drinking of milk and after four hours followingthe drinking of the milk) and an expired gas and a gas obtained from theleft hand of Subject B (before the drinking of milk and after four hoursfollowing the drinking of the milk).

FIG. 8 is an illustration showing chromatograms of hydrogen contained inexpired gas. Chromatogram a is obtained by measuring the hydrogencontent in expired gas of Subject A before the drinking of milk, andChromatogram b is obtained by measuring the hydrogen content in expiredgas of Subject A after the drinking of milk. In FIG. 8, Chromatograms(a) and (c) are obtained with a sensitivity of 5 mV and Chromatograms(b) and (d) are obtained with a sensitivity of 100 mV.

FIG. 9 is an illustration showing the analysis results of skin permeablegas obtained from left hands for ten minutes. The gas was obtained afterabout four hours since subjects had drunk milk. In FIG. 9, thesensitivity is 2 mV.

It is clear from these figures that human skin surface emanates hydrogenand the hydrogen can be detected using a device of the presentinvention. It is found that the correlation between the ingest of milkand the hydrogen emanation can be clarified.

When the hydrogen content in gas obtained before the drinking of milk iscompared with the hydrogen content in gas obtained after about fourhours following the drinking of milk, the following results areobtained: the hydrogen content in expired gas of Subject A increasesfrom 2 to 7 ppm, the hydrogen content in expired gas of Subject Bincreases from 1 to 91 ppm, the hydrogen content in gas emanating fromthe left hand of Subject A increases from 0.003 to 0.08 ppm, and thehydrogen content in gas emanating from the left hand of Subject Bincreases from 0.07 to 0.41 ppm. Thus, it is clear that an increase inhydrogen in not only expired gas but also gas emanating from a left handis caused by the drinking of milk. Furthermore, it is clear from thismeasurement that there is an extremely high correlation between thehydrogen content in expired gas and the hydrogen content in gasemanating from skin.

FIGS. 10 and 11 are illustrations showing a correlation between expiredgas and skin permeable gas. There is a obvious correlation for hydrogen,which suggests that diagnosis using the skin permeable gas is possible.

FIG. 12 is an illustration showing a configuration of a skin permeablegas-measuring apparatus according to a fifth example of the presentinvention.

In this figure, reference numeral 50 represents a skin permeablegas-measuring apparatus, reference numeral 51 represents a skinpermeable gas-collecting chamber, reference numeral 52 represents acirculating chamber, reference numeral 53 represents a blower fan,reference numeral 54 represents various coloring agents A, B, C, andreference numeral 55 represents skin of a subject.

As shown in this figure, skin permeable gas is collected on the skin 55,the collected skin permeable gas is then immediately circulated to allowthe gas to pass through the various coloring agents 54, therebydetecting specific gas. Thus, the subject can obtain the measurementresult on the spot.

Information processing of a sampling detection system disposed on skincan be performed with a computer, which is not shown.

In order to prevent gas from being absorbed in H₂O in sweat, gasreplacement is sufficiently performed. That is, it is critical that usedgas is removed by ventilation and sample gas is collected while thesample gas is successively discharged.

The use of the present invention is described below.

A correlation between skin permeable gas and morbidity is as follows.The skin permeable gas has a correlation with diabetes, obesity, andautointoxication when the skin permeable gas is acetone, and the skinpermeable gas has a quantitative correlation with the presence ofenteric bacteria that decompose lactose when the skin permeable gas ishydrogen. Furthermore, the skin permeable gas has a correlation withuremia, liver failure, abdominal abscess, and the presence ofhelicobacter pylori when the skin permeable gas is ammonia. As describedabove, the measurement of the skin permeable gas according to thepresent invention can be contribute to the diagnosis of various types ofmorbidity.

It should be understood that the present invention is not limited to theabove examples and various modifications may be performed within thescope of the present invention. The present invention is intended tocover such modifications.

As described above in detail, according to the present invention, thefollowing advantages can be obtained.

(A) Clinical information that are useful for in-home medical care andhealth management can be obtained by noninvasive and bloodlessoperations.

(B) Skin permeable gas emanating from skin surface can be readilycollected and the species and quantity of such gas can be analyzed.

(C) Collected gas can be readily stored in a sealed manner and thentransported to a measuring apparatus.

(D) Secure attachment to skin is possible.

(E) Contaminants contained in the space of a cylindrical member and/orleaking from the surroundings can be measured in advance and thereforethe skin permeable gas can be precisely analyzed.

(F) When a spiral groove is placed, the quantity of collected gas perunit area of skin can be increased and thus the skin permeable gas canbe efficiently collected.

(G) The miniaturization of a device and apparatus is possible.

INDUSTRIAL APPLICABILITY

As described above, a skin permeable gas-collecting device and skinpermeable gas-measuring apparatus of the present invention are usefulfor clinical measurement using skin permeable gas and useful indetermining human health condition. Such a device and apparatus can beminiaturized and are fit for the simple diagnosis of various types ofmorbidity.

1-6. (canceled)
 7. A device for collecting skin permeable gas,comprising: (a) a cylindrical member including a spiral groove; (b) acover disposed on the upper surface of the cylindrical member; (c) agas-introducing section connected to the cover; (d) a gas deliverysection connected to the cover; and (e) a sealing member for sealing thegroove of the cylindrical member and for maintaining air contained inthe groove at a predetermined temperature, (f) wherein, after componentsin the air maintained at a predetermined temperature are analyzed, thesealing member is detached from the cylindrical member and thecylindrical member from which the sealing member is detached is thenbrought into intimate contact with skin of a subject to collect the skinpermeable gas.